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Pharmatest Services Ltd

Pharmatest Services Ltd (Pharmatest) is a contract research organization (CRO) specialized in clinically predictive preclinical efficacy services in the therapeutic areas of oncology and skeletal diseases.

Our services have been developed with just one goal in mind – to make your nonclinical drug development faster and more predictive. Our mission is to reduce the amount of drug candidates failing in clinical trials. Outsource your preclinical efficacy testing to Pharmatest and increase significantly the speed of your drug development with reduced costs.

Partnering with Pharmatest gives you an on-demand access to latest translational tools for lead validation and proof-of-concept studies in oncology and skeletal diseases.

Pharmatest Services Ltd (Pharmatest) is a contract research organization (CRO) specialized in clinically predictive preclinical efficacy services in the therapeutic areas of oncology and skeletal diseases.

Our services have been developed with just one goal in mind – to make your nonclinical drug development faster and more predictive. Our mission is to reduce the amount of drug candidates failing in clinical trials. Outsource your preclinical efficacy testing to Pharmatest and increase significantly the speed of your drug development with reduced costs.

Partnering with Pharmatest gives you an on-demand access to latest translational tools for lead validation and proof-of-concept studies in oncology and skeletal diseases.

Pharmatest offers in vitro cancer cell assays that can be used for fast demonstration of efficacy of test compounds. Cell proliferation and viability can be determined using CellTiter-GloTM... Show more »

Cancer cell proliferation and viability assays

Cancer cell apoptosis and cytotoxicity assays

Cancer cell invasion assays

Pharmatest offers in vitro cancer cell assays that can be used for fast demonstration of efficacy of test compounds. Cell proliferation and viability can be determined using CellTiter-GloTM luminescent cell viability assay. Cytotoxicity can be determined using the CellToxTM Green fluorescence-based cytotoxicity assay, and apoptosis can be measured using several methods. Cell invasion is determined using a system where cancer cells are grown on a basement membrane-like MatrigelTM coated filter chamber, and their capacity to migrate through the Matrigel layer is determined.

We offer studies from high-throughput screening of a large number of test compounds to extensive studies that will confirm the efficacy and allow calculating EC50 values for the test compounds. The extensive studies will demonstrate what cancer cell lines are affected by the test compounds, and the efficacy can then be confirmed in vivo in our animal models using the same cancer cell lines that were affected by the test compounds in vitro.

In oncology Pharmatest is specialized in orthotopic and metastasis models, and our special expertise is in bone metastasis models. The... Show more »

Breast cancer (with MDA-MB-231(SA), 4T1, BT-474, MCF-7 cells)

Prostate cancer (with LNCaP, VCaP, PC-3 cells)

Multiple myeloma (with 5TGM1 cells)

Pancreatic cancer (with BxPC3 cells)

In oncology Pharmatest is specialized in orthotopic and metastasis models, and our special expertise is in bone metastasis models. The major advantage of these models is the proper tissue microenvironment that is known to affect tumor growth, metastasis and drug resistance. This increases substantially the clinical relevance and predictivity over traditionally used subcutaneous models that lack the proper microenvironment.

Pharmatest offers both xenograft and syngeneic cancer models in mice. Xenograft models include using human cancer cell lines, which requires using immunocompromised mice. Syngeneic models include using mouse cell lines that allow using mice with normal immune system, allowing to test immunomodulators. Pharmatest is also developing novel models using humanized mice that have human immune system, allowing to test immunomodulators using human cancer cells.

Pharmatest can also assist our customers in finding and selecting appropriate patient-derived xenograft (PDX) models from the many providers of PDX models. Our experts will find the best PDX models for the purpose of the customer, and Pharmatest can manage the projects. The customer needs only to contact and communicate with Pharmatest, and Pharmatest will subcontract the PDX studies to the providers, take care of all correspondence with the PDX providers, and prepare a summary report including all results for the customer.

Pharmatest’s in vitro bone cell culture assays that can be used for fast demonstration of efficacy of test compounds. We offer studies from preliminary... Show more »

Osteoclast differentiation assay

Osteoclast activity assay (bone resorption assay)

Osteoblast differentiation assay

Osteoblast activity assay (bone formation assay)

Pharmatest’s in vitro bone cell culture assays that can be used for fast demonstration of efficacy of test compounds. We offer studies from preliminary testing of a large number of test compounds to extensive testing that will confirm the efficacy and allow calculating EC50 values for the test compounds.

Our bone cell culture assays can be conveniently used for identifying compounds with best efficacy for subsequent testing in animal studies. They include assays for demonstrating direct anabolic effects on activity or differentiation of bone forming osteoblasts and direct anti-resorptive effects on activity or differentiation of bone resorbing osteoclasts.

Osteoclast assays are available in human, rat and mouse cells. Human osteoclast cultures are performed using CD34+ human osteoclast precursor cells. Osteoclast differentiation is quantitated by measuring tartrate-resistant acid phosphatase isoform 5b activity (TRACP5b) released into the culture medium, and bone resorption activity of the formed mature osteoclasts is quantitated by measuring C-terminal cross-linked telopeptides of type I collagen (CTX-I) released into the culture medium.

Osteoblast assays are performed using the mouse mesenchymal progenitor cell line KS483 that is allowed to differentiate into mature osteoblasts capable of forming bone nodules. Osteoblast differentiation is quantitated by measuring alkaline phosphatase activity from the cell lysates, and bone formation activity of the formed mature osteoblasts is quantitated by measuring procollagen I N-terminal propeptide (PINP) released into the culture medium.

For the follow-up and endpoint measurements available in these models please check the Service “Bone analysis”.

With the osteoporosis animal models Pharmatest offers specially designed study setups for testing anti-catabolic and anabolic compounds in prevention and treatment settings. Our projects can range from less extensive preliminary studies to regulatory studies performed according to the guidelines of FDA and EMA. We have also designed special project types for testing biosimilars and functional foods that have less extensive regulatory requirements.

Osteoarthritis (OA) models of Pharmatest include models where OA is induced chemically (Rat MIA model) or surgically (MMT+MCLT, ACLT, pMMx, and ACLT+pMMx models). The MIA model is considered a model of OA-induced pain, while the surgical models are more suitable for studying effects on OA-related cartilage and bone destruction.

Follow-up and endpoint measurements available include pain measurements and cartilage and bone analyses with various methods. One key endpoint measurement is microscopic evaluation of degenerative changes in operated knee joints according to the recommendations of the Osteoarthritis Research Society International (OARSI) histopathology initiative.

Bone health is affected by several factors, including age, physical activity, diseases,... Show more »

Intact rats and mice

Rat and mouse ovariectomy (OVX) models

Rat and mouse orchidectomy (ORX) models

Mouse model of glucocorticoid-induced osteoporosis (GIO)

Characterization of bone phenotype in genetically modified mice

Bone health is affected by several factors, including age, physical activity, diseases, medication, various hormonal, lifestyle and nutrition conditions, and genetic defects and modifications. All these factors may induce either beneficial or adverse effects on bone safety. Pharmatest can help you determine bone safety of your new drug candidates, biosimilars, functional foods, nutrition supplements and other substances.

Pharmatest’s standard study setups in different disease models include different combinations of the following bone analysis methods that can also be used as stand-alone services, where you just send us your samples and we will perform the selected measurements and provide you with the results:

Pharmatest’s standard study setups in different disease models include different combinations of the following bone analysis methods that can also be used as stand-alone services, where you just send us your samples and we will perform the selected measurements and provide you with the results:

The measurements are performed in serum samples using the IDS-iSYS automated platform (IDS, Boldon, UK). We also offer measurements of other bone-related biomarkers using manual methods (please ask for further information).

The measurements are performed in serum samples using the IDS-iSYS automated platform (IDS, Boldon, UK). We also offer measurements of other bone-related biomarkers using manual methods (please ask for further information).

The in vitro androgenic assay is performed using the PSA-expressing androgen-sensitive human prostate cancer cell line LNCaP. Cell proliferation is determined using CellTiter-GloTM luminescent cell... Show more »

Androgenic assay using LNCaP human prostate cancer cells

Estrogenic assay using mouse mesenchymal progenitor cell line KS483

The in vitro androgenic assay is performed using the PSA-expressing androgen-sensitive human prostate cancer cell line LNCaP. Cell proliferation is determined using CellTiter-GloTM luminescent cell viability assay (CTG). Secreted PSA levels in the conditioned medium can also be measured.

The in vitro estrogenic assay is performed using the mouse mesenchymal progenitor cell line KS483 that is allowed to differentiate into mature osteoblasts capable of forming bone nodules. Osteoblast formation is quantitated by measuring alkaline phosphatase activity from the cell lysates, and bone formation activity of the formed mature osteoblasts is quantitated by measuring procollagen I N-terminal propeptide (PINP) released into the culture medium.

The Hershberger bioassay is designed to identify suspected androgens and antiandrogens (either drug candidates or endocrine disruptors) based on changes in the weights of five androgen-responsive tissues. The uterotrophic bioassay identifies estrogenic or anti-estrogenic compounds (either drug candidates or endocrine disruptors) based on their effects on wet and blotted uterus weight.

There are several advantages in using these OECD-validated assays:
- The weighted target tissues are the natural targets for androgens/estrogens
- The tissue growth response is relatively rapid
- The tissue weights are quantitative

Co-development of novel models with a customer, funded by the customer

The investment is returned as price reductions when the new model is used by the customer

Pharmatest is allowed to offer the developed model freely to our other customers

Long-term outcome: An entire R&D department available for our customers... Show more »

Co-development of novel models with a customer, funded by the customer

The investment is returned as price reductions when the new model is used by the customer

Pharmatest is allowed to offer the developed model freely to our other customers

Long-term outcome: An entire R&D department available for our customers free of charge!

Model development is also available for exclusive use for the funding customer (please ask for details).

All co-development projects receive a top priority in our R&D pipeline.

Even though we keep a constant eye on the early drug discovery field and do our best to maintain a broad and ranging service portfolio, you may find that you need a particular model that we do not have. In a case like this, we offer you an option for a co-development project. This is a concept we have used with great success to provide our customers with a fast-track access to completely new models.

Those customers who have extensive use for one of our models can also in-license that particular model or assay. Instead of working with us on a project basis, we can transfer the entire model to your laboratory, provide you with all necessary documentation (SOPs) related to the model, including all future updates, and train your personnel to use the model according to the SOPs.